Influence of Pregnancy and Oral Contraceptives on Platelets in Relation to Coagulation ancl Aggregation^[*]

Summary

Holtzman rats, 16 to 19 days pregnant, exhibited in vitro hypercoagulability with a 27 % reduction in the plasma clotting time (PCT) (siliconized and plastic) as compared to non-pregnant controls. This hypercoagulability was entirely due to an increased activity of platelet factor 3, since a comparable reduction in the clotting time was obtained when the washed platelets from these animals were resuspended in a standard platelet-poor plasma. In contrast to this, when the platelets in the original plasma were replaced by a phospholipid suspension, the clotting time in plastic but not in glass, was prolonged in pregnant rats, suggesting a decreased activity of the contact system. In addition, the pregnant rats exhibited a marked increased susceptibility of platelets to thrombin and to ADP-induced aggregation.

In 6 pregnant women and in 9 women taking contraceptives, a highly significant in vitro hypercoagulability was also present, since the PCT was decreased 26% and 22%, respectively, as compared to the 14 controls. This hypercoagulability appeared to be entirely due to the increased activity of platelet factor 3 as in rat. However, the clear-cut increased susceptibility of platelets to thrombin and ADP-induced aggregation noted in the pregnant rats was not obtained in either the pregnant women or in the women taking contraceptives.

^* This work was presented in part at the Annual Meeting of the International Academy of Pathology, Montreal, Canada, March 1971.

⁺ Present address : Director, INSERM, Unité, 22 Avenue du Doyen Léne, 69500 Lyon- Bron, France.

• References

• 1 Dugdale M, Masi A. T. 1971; Hormonal contraception and thromboembolic disease: Effects of the oral contraceptives on hemostatic mechanisms. A review of the literature. Journal of Chronic Diseases 23: 775.
• 2 Egebeeg O, Oween P. A. 1963; Oral contraception and blood coagulability. British Medical Journal 01: 220.
• 3 Inman W. H. W, Vessey M. P, Westeeholm B, Engeltod A. 1970; Thromboembolic disease and the steroidal content of oral contraceptives. A report to the committee on safety of drugs. British Medical Journal 02: 203.
• 4 Keown D. 1969; Review of arterial thrombosis in association with oral contraceptives. British Journal of Surgery 56: 486.
• 5 Margulis B. R, Ambeus J. L, Mink I. B, Stryker J. C. 1965; Progestational agents and blood coagulation. American Journal of Obstetrics and Gynecology 93: 161.
• 6 Markush R. E, Seigel D. G. 1969; Oral contraceptives and mortality trends from thromboembolism in the United States. American Journal of Public Health 59: 418.
• 7 Nilsson I. M, Kullander S. 1967; Coagulation and fibrinolytic studies during pregnancy. Acta Obstetrica et Gynecologica 46: 273.
• 8 Penick G. D, Dejanov I. I, Roberts H. R, Websteh W. P. 1966; Elevation of factor VIII in hypereoagulable states. Thrombosis et Diathesis Haemorrhagica Suppl. 20: 39.
• 9 Poller L, Thompson M. 1966; Clotting factors during oral contraception : Further report. British Medical Journal 02: 23.
• 10 Renaud S. 1969; The recalcification plasma clotting time. A valuable general clotting test in man and rats. Canadian Journal of Physiology and Pharmacology 47: 689.
• 11 Renaud S, Lecompte F. 1970; a Thrombosis prevention by coagulation and platelet aggregation inhibitors, in hyperlipemic rats. Thrombosis et Diathesis Haemorrhagica 24: 577.
• 12 Renaud S, Lecompte F. 1970; b Hypercoagulability induced by hyperlipemia in rat, rabbit and man. Role of platelet factor 3. Circulation Research 27: 1003.
• 13 Renaud S, Kuba K, Goulet C, Lemire Y, Allard C. 1970; Relationship between platelet fatty acid composition and platelet aggregation in rat and man, in connection with thrombosis. Circulation Research 26: 553.
• 14 Renaud S, Gautheron P, Rosenstein H. 1973 Platelet factor 3 activity in washed platelets. Thrombosis et Diathesis Haemorrhagica (sent for Publication).
• 15 Sise H. 1968. Anovulatory hormones and blood coagulation. In: Astrup T, WRIGHT I. S. . (eds.) Blood Coagulation, Thrombosis, and Female Hormones. The James F; Mitchell Foundation, Washington, D.C., IT. S.A.,: 19.
• 16 Walsh P. N. 1972; The effect of dilution of plasma on coagulation : The significance of the dilution-activation phenomenon for the study of platelet coagulant activities. British Journal of Haematology 22: 219.